Cathepsin K is a cysteine protease expressed predominantly in osteoclasts

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All authors Crizotinib NSCLC read and approved the final manuscript.AcknowledgementsThe authors would like to thank Jo-Yu Hsu for providing the assist in the statistical analysis. Written consent for publication was obtained from the patient or their relative. There was no source of support for this study.Mortality is the most clinically relevant and commonly used primary outcome measure for phase III trials in intensive care. However, the optimal duration of follow-up for the determination of mortality in such trials is uncertain [1,2]. Interventional ICU trials have followed up patients for different durations [3-7]. Furthermore, some trials have censored follow up at time of hospital discharge ignoring any subsequent out-of-hospital deaths [8,9].

Such variability creates confusion, leads to controversy and makes meta-analyses of trials with different times of mortality assessment difficult to interpret. Measurement of mortality at 28-days or censoring at hospital discharge have logistic advantages but as many as one-third of critically ill patients may still be in hospital after 28 days and deaths can still occur soon after hospital discharge [3]. Longer follow up time, however, may make it difficult to distinguish between the effects of critical illness (or the studied interventions) from those of underlying age and co-morbidities [10]. Follow up for longer time periods, especially where this extends beyond hospital discharge, is more difficult and costly.

The ideal period of follow up would be up to a time point by which the effects of critical illness remain powerful independent determinants of outcome and before pre-existing factors, such as age and co-morbidity, can have a marked and confounding impact on survival [11].The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE) Adult Patient Database (APD) gathers information about the vast majority of admissions of critically ill patients from various intensive care units (ICUs) across Australia and New Zealand but currently does not follow up patients beyond hospital discharge [12]. However, in an embedded cohort of ICU patients treated at the Royal Perth Hospital, which is a large university teaching hospital in Western Australia (WA cohort), such information is available [11].

Western Australia is geographically isolated and has a low rate of emigration [11] and, as such, loss to medium-term and long-term survival follow-up by the Western Australian Death Registry is very low [13].We hypothesized that, if the characteristics and short-term outcomes of patients in the WA cohort and the various ICUs from Australia (as identified within the two databases) were comparable, then the follow-up data of the patients in WA cohort could be used to estimate the likely in-hospital Batimastat and out-of-hospital long-term survival of critically ill patients in Australia.